The Research On Sevoflurane Inhibits Memory Consolidation Through PICK1/ERK1/2/GSK3 β Signaling

Objective: To examine the effects of sevoflurane on memory consolidation,and the role of PICK1/ERK1/2/GSK3β signaling pathway.Methods: For in vivo study,the C57BL/6 PICK1 knock-out mice were exposed to 2% sevoflurane for 2 h.The hippocampal tissues were collected for detecting the protein expressions of PICK1,ERK1/2,P-ERK1/2,GSK3β and P-GSK3β by western blot.For in vitro study,the primary hippocampal neurons were treated with phospho-ERK1/2 activator Honokiol or/and PICK1 inhibitor FSC231 before sevoflurane exposure(2%,3 h).Neurons were harvested for detection of P-GSK3β protein level.For behaviour study,the PICK1 knock-out mice were administrated with 2% sevoflurane for 3 h.The open-field test and inhibitory avoidance task were enrolled for evaluation of motor activity and memory consolidation respectively.Results:The protein levels of PICK1,P-ERK1/2 and P-GSK3β were depressed in sevoflurane or PICK1 knock-out group.Compared with sevoflurane group,the expressions of P-ERK1/2 and P-GSK3β were further decreased in sevoflurane plus PICK1 knock-out group.For in vitro study,the expression of P-GSK3β was inhibited by sevoflurane exposure,which could be improved by application of Honokiol.Moreover,the improvement of P-GSK3β by Honokiol could be reversed by further addition of FSC231.Finally,analysis of behaviour study showed that sevoflurane treatment or PICK1 knock-out did not alter the motor activity.However,sevoflurane administration inhibited memory consolidation.For the knock-out mice,the memory consolidation was further suppressed by sevoflurane exposure.Conclusion:Sevoflurane could inhibit memory consolidation,and the PICK1/ERK1/2/GSK3β signaling pathway may be involved in this process.